Immunology III: Innate Immunity & Inflammation 2 (Part 3: Inflammatory mediators)

Question 1

Major pro-inflammatory cytokines CHART

Answer 1

Question 2

IL-1 – important cellular sources:

Answer 2

Macrophages/monocytes, dendritic cells, keratinocytes, epithelial cells, endothelial cells

Question 3

TNF-alpha – important cellular sources

Answer 3

Macrophages/monocytes, dendritic cells, mast cells, NK cells, epithelial cells

Question 4

IL-6 – important cellular sources

Answer 4

Macrophages/monocytes, dendritic cells, NK cells, epithelial cells, endothelial cells

Question 5

IL-1, TNF-alpha, IL-6: what are their redundant and pleiotropic effects?

Answer 5

Redundant – functions overlap between these cytokines
Pleiotropic – many effects for each cytokine

Hint: just remember the functions IL-6 doesn’t perform*

Question 6

What functions does IL-6 not perform?

Answer 6

It does NOT:
1.) increase vascular permeability
2.) Produce chemokine (CXCL-8)
3.) Produce IL-6

Question 7

Fever and acute inflammation. What temp. is considered a fever? What are the mechanisms of a higher body temp? What are the benefits of a fever?

Answer 7

Temperature above 37.7 Celsius

Caused by changing the hypothalamic set-point – your hypothalamus now “thinks” that your normal temperature is higher
Mechanisms of higher body temperature:
Peripheral vasoconstriction  blood flow away from the periphery, to the core  less heat loss
Shivering
Increased metabolic rate

Benefits to fever?
Adaptive immune mechanisms in general are more effective at higher temperatures

The hypothalamic set-point is altered by increased levels of pro-inflammatory cytokines
IL-1 and TNF- can induce fever at low serum concentrations
IL-6 induces fever at higher (10X) concentrations (less potent)
Pro-inflammatory cytokines cause elevation of prostaglandin E2 production by cells in the 3rd ventricle (FYI - area called the OVLT)
PGE2 leads to signaling that changes the hypothalamic setpoint
Why blockers of cyclooxygenase activity (Tylenol, ibuprofen) are effective anti-pyretics

Question 8

Acute phase proteins

Answer 8

Elevated levels of inflammatory cytokines – IL-6 in particular - cause the liver to increase the secretion of useful (from an acute inflammation perspective) proteins into the bloodstream
Known as acute phase proteins

Major acute phase proteins include:
C-reactive protein (CRP)
Opsonin that binds to phosphorylcholine – a component of bacterial cell walls
It can also activate C1q, and thus trigger the classical complement cascade when it binds to phosphorylcholine
CRP is a common lab measurement ordered to diagnose inflammatory disease

Question 9

What are the 4 major acute phase proteins?

Answer 9

Ferritin
Binds to serum iron with high affinity – many microbes depend on iron for their metabolism, and ferritin sequesters it from these microbes
Hepcidin
Interferes with intestinal transport of iron into the bloodstream – this also sequesters iron from microbes
Mannose-binding lectin (MBL) – we’ve seen this as the PRR that initiates the lectin complement cascade
Serum amyloid protein A (SAA) – complicated molecule
Modulates (usually increases) the activation of the inflammasome and TLRs
Opsonizes some gram-negative bacteria

Question 10

Ferritin: What does it do?

Answer 10

Binds to serum iron with high affinity – many microbes depend on iron for their metabolism, and ferritin sequesters it from these microbes

Question 11

Hepcidin: What does it do?

Answer 11

Interferes with intestinal transport of iron into the bloodstream – this also sequesters iron from microbes

Question 12

Mannose-binding lectin (MBL): What does it do?

Answer 12

Initiates the lectin complement cascade

Question 13

Serum amyloid protein A (SAA): What does it do?

Answer 13

Modulates (usually increases) the activation of the inflammasome and TLRs

Opsonizes some gram-negative bacteria